The applicant proposes to study the ability of mice different ages of control infections of Trypanosoma musculi, a mouse-specific parasite, and to compare age-associated changes in relative susceptibility in two strains of mice one of which (A/He) is inherently more susceptible than the other, C57BL/6 (B/6) strain. The investigation will begin with experiments designed to reveal the immune mechanism employed by mice to clear T. musculi infections. The procedures will include transfer of protective immunity to parasites from donors to optimally-irradiated recipients and an in vitro assay for antibody-dependent and -independent cytotoxic effector cells. The development and relative magnitude of protective immunity afforded by spleen cells from normal, infected and recovered ("cured") donors during the course of infection and subsequent recovery will be analyzed. The role of humoral antibodies acting in concert with effector cells will be determined. Effector cells will be identified. A series of studies of immunity to T. musculi in aged A/He and B/6 mice will follow. Changes in effector cell capacity and in quality and/or quantity of facilitating humoral antibodies to T. musculi will be evaluated. The influence of the aged milieu ("internal environment") on the functional capability of protective effector mechanisms will be explored. These investigations will (a) contribute significantly to knowledge concerning immunity to parasites, (b) provide missing information about the capability of the aged immune system to react against animal parasites, and (c) be among the first to consider natural resistance to parasites in aging host populations.